ASHM Report Back

Clinical posts from members and guests of the Australasian Society for HIV, Viral Hepatitis and Sexual Health Medicine (ASHM) from various international medical and scientific conferences on HIV, AIDS, viral hepatitis, and sexual health.

How would you like your PrEP

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No HIV practitioner can avoid the onslaught of PrEP. Whether you like it or not, you'll be facing it head on from fellow doctors and patients alike. Yet there are too many vital questions unanswered. Today's session on "How would you like your PrEP" introduces HPTN 067 or ADAPT study that attempts to address the question of optimal dosing and schedule of daily vs "time driven" ( 2 tabs a week + post exposure dose) and "event driven" ( one before and one after). Equally important is the question regarding how to start and stop PrEP ie how many days after starting and stopping PrEP is an individual protected from acquiring HIV.

 
ADAPT STUDY or HPTN 067
 
were conducted in Harlem (US), Silom (Bangkok, Thailand) and Cape Town (South Africa), designed to measure the coverage of sex events, number of tablets (required and taken) and self reported side effects and secondarily, adherence, safety and HIV infections. In other words, it is designed to identify dosing schedules that participants are more likely to follow and if these schedules "influence healthier sexual practices".
 
Apart from the U.S. site, the speakers concluded that Truvada PrEP "coverage" were comparable across the arms although daily dosing proved to produce better adherence. It is important to note that " comparable coverage" in this context does NOT equate to "comparable efficacy". If proven efficacious it will provide easier/cheaper alternative to daily dosing.
 
 
IPERGAY PK SUBSTUDY
 
12 participants received a single double dose TDF/FTC followed by PK sampling of plasma, PBMC, DBS and saliva done at T0, 0.5, 1, 2, 4, 8 and 24 hours.
10 participants had 2 rectal biopsies (including T0) and 2 participants had rectal biopsies at the above time schedule. 
Rectal biopsies were then exposed overnight to CCR5 tropic HIV 1 virus.
 
High concentrations (comparable to ART drug levels) of FTC were detected early at around T0.5 and for TDF at around 24 hours after dosing. However, although all the rectal biopsies were "infected" at baseline this compares to 6/10 of infected biopsies taken after dosing. Unfortunately there were no rectal PK and "infectivity" analysis done with additional post exposure doses to determine the protection conferred by the second and 3rd doses in the Ipergay PrEP regimen.
 
CELL PREP
 
This study extrapolates PrEP protective intracellular concentrations from STRAND and iPREX. 
Participants were given daily TDF/FTC for 30 days to 19 volunteers and bloods taken at days 1,3,7,20,30 and 35,45,60.
Estimated risk reductions were found to be
After dose 1 - 77%
After dose 2- 89%
After dose 3 - 98%
After dose 4 - 98%
Stop +1d - 97%
Stop +3d - 96%
Stop +5d - 93%
Stop +7d - 90%
 
Putting all these together, I believe that we should continue to advocate for daily dosing as it encourages better adherence and good coverage. Patients should continue to use condoms for at least the first 3 doses.
 
However, stopping PrEP continues to be unclear. IPrex rectal PK substudy showed 6 out of 10 "infected" samples after 24 hours despite CellPrEP showing 96% risk reduction up to 3 days after stopping daily dosing. I guess the question remains as to what the period of infectivity is after a mucosal exposure/inoculum.
 
 
Tagged in: IAS2015
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Guest Sunday, 19 November 2017

Please join us for a memorial event celebrating the life of one of Australia’s leading HIV advocates, Levinia Crook… https://t.co/N7dof5xaGa

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